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Sulfonamide-induced cutaneous drug r...

Vyas, Piyush Manhar.

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Sulfonamide-induced cutaneous drug reactions: Role of bioactivation, oxidative stress and folate deficiency.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Sulfonamide-induced cutaneous drug reactions: Role of bioactivation, oxidative stress and folate deficiency./
Author:	Vyas, Piyush Manhar.
Description:	179 p.
Notes:	Adviser: Craig K. Svensson.
Contained By:	Dissertation Abstracts International67-10B.
Subject:	Health Sciences, Pharmacy. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3239327
ISBN:	9780542930409

Sulfonamide-induced cutaneous drug reactions: Role of bioactivation, oxidative stress and folate deficiency.
Vyas, Piyush Manhar.

Sulfonamide-induced cutaneous drug reactions: Role of bioactivation, oxidative stress and folate deficiency. - 179 p.

Adviser: Craig K. Svensson.

Thesis (Ph.D.)--The University of Iowa, 2006.

Sulfonamide- and sulfone-induced hypersensitivity reactions are thought to be mediated through bioactivation of parent drug molecule(s) to their respective reactive metabolite(s). In order to explain the cutaneous drug reactions caused by sulfonamides and sulfone, a mechanism can be proposed by which the bioactivation of these drugs in keratinocytes of the skin forms reactive hydroxylamine metabolites that can covalently bind to cellular proteins, which in turn act as antigens leading to the cascade of immune reactions resulting in a cutaneous drug reaction.

ISBN: 9780542930409Subjects--Topical Terms:

1017737
Health Sciences, Pharmacy.

Sulfonamide-induced cutaneous drug reactions: Role of bioactivation, oxidative stress and folate deficiency.
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020 $a 9780542930409
035 $a (UMI)AAI3239327
035 $a AAI3239327
040 $a UMI $c UMI
100 1 $a Vyas, Piyush Manhar. $3 1287145
245 1 0 $a Sulfonamide-induced cutaneous drug reactions: Role of bioactivation, oxidative stress and folate deficiency.
300 $a 179 p.
500 $a Adviser: Craig K. Svensson.
500 $a Source: Dissertation Abstracts International, Volume: 67-10, Section: B, page: 5688.
502 $a Thesis (Ph.D.)--The University of Iowa, 2006.
520 $a Sulfonamide- and sulfone-induced hypersensitivity reactions are thought to be mediated through bioactivation of parent drug molecule(s) to their respective reactive metabolite(s). In order to explain the cutaneous drug reactions caused by sulfonamides and sulfone, a mechanism can be proposed by which the bioactivation of these drugs in keratinocytes of the skin forms reactive hydroxylamine metabolites that can covalently bind to cellular proteins, which in turn act as antigens leading to the cascade of immune reactions resulting in a cutaneous drug reaction.
520 $a In order to probe the proposed mechanism, we determined the enzymes responsible for the bioactivation of these parent drugs to their hydroxylamine metabolites in cultured human keratinocytes. It was found that flavin containing monooxygenases and peroxidases play an important role in the bioactivation of these drugs in keratinocytes. We also confirmed the presence of these enzymes in keratinocytes. Interestingly, though cytochrome P450s are important in the oxidation of parent arylamine xenobiotics to their hydroxylamine metabolites in the liver, they do not appear to play a significant role in the bioactivation of these drugs in keratinocytes.
520 $a The hydroxylamine metabolites of sulfamethoxazole and dapsone can undergo autooxidation, generating reactive free radicals. Our studies showed that both of these metabolites elevate oxidative stress in keratinocytes by forming reactive oxygen species. Though the cytotoxicity induced by these metabolites is not correlated with the extent of oxidative stress, the generation of reactive oxygen species may be important finding as these species can act as danger signals that activate antigen presenting cells in the skin.
520 $a As a possible explanation for the idiosyncratic nature of these reactions, folate deficiency was studied as a potential risk factor. However, the results of these studies suggested that deficiency of folic acid in keratinocytes does not predispose such cells to the toxicity associated with the parent drugs or their metabolites. Unexplored is the potential role of such deficiency on the immune response itself.
590 $a School code: 0096.
650 4 $a Health Sciences, Pharmacy. $3 1017737
690 $a 0572
710 2 0 $a The University of Iowa. $3 1017439
773 0 $t Dissertation Abstracts International $g 67-10B.
790 $a 0096
790 1 0 $a Svensson, Craig K., $e advisor
791 $a Ph.D.
792 $a 2006
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3239327